Contraception method using competitive progesterone antagonists and novel compounds useful therein

Abstract

Competitive progesterone antagonists, including two novel steroids, viz., 11beta,19-[4-(cyanophenyl)-o-phenylene]-17beta-hydroxy-17alpha-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one and 11beta,19-[4-(3-pyridinyl)-o-phenylene]-17beta-hydroxy-17alpha-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one, inhibit formation of endometrial glands at below their ovulation inhibiting dose and the abortive dose, and thus achieve oral contraception in females without adversely affecting the menstrual cycle and without risk of aborting a previous implanted fertilized egg or a fetus.

What is claimed is: 
     
       1. A method for inhibiting the formation of endometrial glands in the proliferation phase as well as the function of the glands in the luteal phase of the menstrual cycle comprising administering a competitive progesterone antagonist at least once before the occurrence of the LH peak in the host female. 
     
     
       2. A method according to  claim 1 , wherein the competitive progesterone antagonist is administered during both the follicular phase and the luteal phase. 
     
     
       3. A method according to  claim 2 , wherein the progesterone antagonist is administered orally about once weekly during each week of the menstrual cycle. 
     
     
       4. A method according to  claim 1 , wherein the competitive progesterone antagonist is
 11β-[(4-N,N-Dimethylamino)-phenyl]-17β-hydroxy-17α-propinyl-4,9(10)-estradien-3-one (RU 38486), 
 11β-[(4-N,N-dimethylamino)-phenyl]-17β-hydroxy-18-methyl-17α-propinyl-4,9 (10)-estradien-3-one, 
 11α-[(4-N,N-dimethylamino)-phenyl]-17aβ-hydroxy-17aα-propinyl-D-homo-4,9(10),16-estratrien-3-one, 
 11β-p-methoxyphenyl-17β-hydroxy-17α-ethinyl-4,9(10)-estradien-3-one, or 
 11β-(4-acetylphenyl)-17β-hydroxy-17α-(prop-1-inyl)-4,9(10)-estradien-3-one. 
 
     
     
       5. A method according to  claim 1 , wherein the competitive progesterone antagonist is
 11β-(4-Dimethylaminophenyl)-17α-hydroxy-17β-(3-hydroxypropyl)-13α-methyl-4,9-gonadien-3-one, or 
 11β-(4-acetylphenyl)-17β-hydroxy-17α-(3-hydroxyprop-1-enyl)-4,9(10)-estradien-3-one. 
 
     
     
       6. A method according to  claim 1 , wherein the competitive progesterone antagonist is
 11β,19-[4-(cyanophenyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one, or 
 11β,19-[4-(3-pyridinyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one. 
 
     
     
       7. A method according to  claim 1 , wherein the progesterone antagonist is administered in individual dosage units every 4 to every 10 days, beginning on any day before the day of ovulation of the first menstrual cycle during which the administration occurs. 
     
     
       8. A method according to  claim 1 , wherein the progesterone antagonist is administered orally. 
     
     
       9. A method according to  claim 1 , wherein the female is a human being. 
     
     
       10. A method according to  claim 1 , wherein the female is a human being and the progesterone antagonist is administered thereto orally every week of each menstrual cycle during which contraception is desired. 
     
     
       11. A method according to  claim 10 , wherein the competitive progesterone antagonist is
 11β,19-[4-(cyanophenyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one, or 
 11β,19-[4-(3-pyridinyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one.